Disease Activity Control of Aflibercept 8 mg in Wet AMD, With Jean-Francois Korobelnik, MD

At the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, Jean-Francois Korobelnik, MD, professor of ophthalmology and head of the ophthalmology department at the University Hospital of Bordeaux, presented a post hoc analysis of the results of the PULSAR phase 3 trial to evaluate the magnitude of disease activity (DA) control with aflibercept 8 mg.1

PULSAR was a 96-week phase 3 trial investigating the safety and efficacy of aflibercept 8 mg in neovascular age-related macular degeneration (nAMD). It was conducted in response to data from the TENAYA and LUCERNE trials, which examined the DA control exhibited by faricimab treatments. This analysis utilized data from PULSAR and DA control criteria from TENAYA/LUCERNE to determine the DA control magnitude accomplished by aflibercept.1

“I am very careful about the interpretation because, as I presented yesterday, [there is] a lot of bias,” Korobelnik told HCPLive. “It’s not exactly the same population of patients. It’s not the same size of the lesions. It’s not the same reading center. It’s very tempting to compare directly, but it is not a head-to-head comparison. Let’s say that it is a suggestion. I think it is helping us, as physicians, understand the trials, but at the same time I think it is preventing us to [reach] a short, robust conclusion.”

At baseline, Korobelnik and colleagues noted that mean choroidal neovascularization (CNV) lesion size was 6.6 mm2 for the aflibercept 8Q16 group in PULSAR and 4.7 mm2 for faricimab in TENAYA/LUCERNE. PULSAR saw 77% of patients with subfoveal CNV at baseline, while TENAYA and LUCERNE had 60% and 63%, respectively.1

The proportion of patients not meeting the DA criteria of TENAYA/LUCERNE 8 or 12 weeks after the last initial treatment dose was 64% for aflibercept 8 mg in PULSAR and 45% for faricimab in TENAYA/LUCERNE. No adjustments were made to compensate for fewer initial doses and more severe baseline DA in PULSAR.1

Korobelnik and colleagues concluded that, despite fewer initial monthly doses, larger baseline lesion size, and requirement for CNV closer to the center, patients who were given aflibercept 8 mg in PULSAR achieved DA control earlier and in higher proportions than those reported for faricimab in TENAYA/LUCERNE.1

Importantly, however, Korobelnik and colleagues urge caution in interpreting the results of this analysis. Although data from TENAYA/LUCERNE and PULSAR were collected and analyzed, no direct comparison between the two studies was made. As a result, any number of potential unidentified limitations, such as demographic variances between study populations and confounding diseases, may distort any direct comparisons made.1

To this end, Korobelnik and colleagues urge further study of the two drugs in direct comparison.

“We analyze the subtypes, the size of the lesions, the disease itself, with all the tools that we have," Korobelnik said. "Is it enough to say that it is the same population or that the differences we detect are all the differences that are there? I think so, but I'm not completely sure. That's why, ideally, there is a need for a true head-to-head trial between the two drugs."

References

1. Korobelnik, J, et al. A PULSAR phase 3 trial post-hoc analysis: Evaluating the timing and magnitude of control of disease activity with aflibercept 8 mg and faricimab, applying similar disease activity criteria across different pivotal Phase 3 trials for nAMD. Abstract presented at Association for Research in Vision and Ophthalmology in Salt Lake City, UT, from May 3 - May 8, 2025.